This website is dedicated to the millions of thyroid patients who are being ignored and left to suffer unnecessarily, and to healthcare practitioners, who want to better serve those patients.

Reply to Dr. Loblay

An OzME subscriber in Australia sent the following post written by a physician.She asked if I would comment on his statements. I did so because in his post, he expressed a view thatI steadfastly disagree with, and because he questioned the ethics of my colleagues and me.

He wrote: I don’t normally consider it appropriate to enter into discussions about various treatments people are trying out. However, I feel it is important to warn you of potential dangers.

I’m not aware of any solid evidence that FMS is a "hypometabolic" condition, and would not advise anyone whose thyroid function is normal euthyroid to take thyroid hormones (T3 tertroxine; T4 – oroxine) unless they have thyroid cancer or multinodular goitre.

At doses of around 200 mcg or above thyroid hormones are likely to cause loss of calcium through the urine, with a long-term risk of osteoporosis. At doses of 300-400 mcg and above there is a risk of developing clinical features of thyrotoxicosis. These include damage to the skeletal and heart muscles. Long-term overuse could lead to muscle wasting, weakness and heart failure.

To find out whether your thyroid function is normal, ask your doctor to do a blood test to check your TSH level (Thyroid Stimulating Hormone). Melatonin is not likely to cause any long-term harm as far as anyone knows at present. However, I think people should be very circumspect about following the advice of a doctor who prescribes thyroid hormones in these circumstances.

Many professionals would regard it as bordering on malpractice.

Dr. Robert H. Loblay
Immunology Unit
Department of Medicine, D06
University of Sydney, NSW 2006

Dr. John C. Lowe’ Response:

Dear Dr. Loblay:

I appreciate your apparent motive of informing OzME subscribers of what you consider possible dangers of thyroid hormone therapy. Well-intended as I assume your statements were, they are misguided and inappropriate, and I must take issue with several points you raised.

You wrote that you are not aware of any solid evidence that FMS is a hypometabolic condition. There is ample evidence for this, although there is no accounting for your not being aware of it. I would hope that your inquiries into the nature of various health care conditions would extend beyond the major indexing systems, such as Medline. As a medical editor, I am lamentably aware of the inadequacies of the indexing systems in distributing scientifically-based information to researchers and clinicians across the globe. Some 80% of all biomedical publications are not indexed in Medline. In addition, most indexing systems publish abstracts of only a limited number of publications.

My point is that the entire mass of biomedical information is available to literally no one. Only those claiming omniscience would express surprise at learning of a view he or she had never heard before. The inadequacies of the dissemination of biomedical information seem so obvious to me that I am always puzzled when I hear someone express surprise or disbelief at new information.

To bring yourself up to steam on the subject, you might read our article on euthyroid fibromyalgia in the February, 1997 issue of Medical Hypotheses (this one is in Medline). For the purposes of responding here to your comments, however, I will say that the only comprehensively plausible hypothesis of fibromyalgia at this time is that the features of the condition are a product of inadequate thyroid hormone regulation of gene transcription, whether due to hypothyroidism or cellular resistance to thyroid hormone.

You wrote that you would not advise anyone whose thyroid function is normal ("euthyroid") to take thyroid hormone unless he or she has thyroid cancer or multinodular goitre. Perhaps you are not aware of the phenomenon of cellular resistance to thyroid hormone of euthyroid individuals (those with normal thyroid function test results). One cause of resistance to thyroid hormone is mutant T3 receptors that have a low affinity for the hormone. Studies using molecular biology techniques have shown why most of these patients, who have hypothyroid-like symptoms, recover only when they use relatively large (supraphysiologic) dosages of T3.

In some of our research patients, dosages have ranged from 75 mcg of T3 to as much as 300 mcg. The highest dosages on record necessary to free resistance patients from their symptoms is 500mcg of T3 and 1000 mcg of T4. Yet, these dosages do not cause tissue thyrotoxicosis in these patients. We have conducted 5 studies with euthyroid fibromyalgia patients (3 were blinded studies) over the past several years. We have done extensive testing with bone densitometry, serial ECGs, and serum and urine tests to detect toxicity of heart, bone, liver, and muscle. But we have found no adverse tissue effects. What we have clearly demonstrated in these studies is that euthyroid fibromyalgia patients have peripheral cellular resistance to thyroid hormone. We do not know the cause of the resistance yet, but it is certain at this time that these patients have cellular resistance to thyroid hormone. We are in the planning stages now of setting up a genetics and molecular biology laboratory to try to identify the mechanism of the resistance. I wonder, would you deny these patients thyroid hormone, in line with your advice to OzME subscribers, because they are euthyroid and do not have thyroid cancer or multinodular goitre?

With the treatment protocol we use, our hypothyroid fibromyalgia patients typically recover even more readily than our euthyroid fibromyalgia patients. What we do to alleviate the fibromyalgia symptoms and signs of these patients is merely raise their dosage of T4 into the range that you warned patients not to take==200 to 400 mcg (0.2 to 0.4 mg). Contrary to your warning, however, extensive testing has shown that these dosages cause no tissue thyrotoxicity in our hypothyroid patients, just as with our euthyroid patients on T3. In both the euthyroid and hypothyroid patients, the serum TSH levels are suppressed, but I emphasize, with no adverse tissue effects whatsoever.

I bring this up because of your warning that dosages over 200 mcg (0.2 mg) are likely to cause adverse effects. You listed loss of calcium through the urine, with a long-term risk of osteoporosis.

You also wrote: At doses of 300-400 mcg and above there is a risk of developing clinical features of thyrotoxicosis. These include damage to the skeletal and heart muscles.

Long-term overuse could lead to muscle wasting, weakness and heart failure." It is true that some patients’ tissues may be overstimulated at these dosages. Because of this, we evaluate each patient as an individual to assure his or her safety. Nevertheless, your statements ar highly misleading and are not supported by the scientific literature.

First, the argument that dosages of thyroid hormone that suppress the TSH level (usually dosages over 200 mcg) cause loss of calcium in the urine simply is not true in general. There may be a slight increase in bone turnover. This is indicated in some of our patients by an increase in the urine levels of hydroxyproline or N-telopeptides. But seldom do T4 dosages as high as 300-400 mcg cause an increase in serum or urine calcium, phosphorus, alkaline phosphatase, or creatine. What’s more, studies during this decade have shown that the increase in bone turnover (indicated by increases in hydroxyproline or N-telopeptides) is not associated with a decrease in bone density, and certainly not with the development of osteoporosis that you propose. The increase in bone turnover occurs during the first year a patient begins taking thyroid hormone, but then the turnover ceases. In the 1980s, some researchers tested patients only during the first year after they had started using T4. They found increased bone turnover and argued fallaciously that this portended osteoporosis and an increased rate of fractures.

When other researchers tested patients between 1 and 2 years after starting T4, they found that the bone turnover had subsided. What this suggests is that hypometabolic tissues such as bone initially have a hypersensitivity to thyroid hormone, but that the hypersensitivity is transient and normalizes after a year or so. We have conducted follow-up testing of fibromyalgia patients who have used thyroid hormone for 1-to-5 years. In general, our patients have bone density above that for age and sex-matched controls. Other researchers have reported the same finding in non-fibromyalgic patients. Some patients taking higher-end dosages have had higher bone density. The increase in bone density is probably a result of the increase in physical activity of the patients after the thyroid hormone medication metabolically capacitates them. (I should note, however, that postmenopausal women who do not take estrogen are at risk for loss of bone density. It is not established, however, that this leads to osteoporosis or progression of bone loss into the fracture risk range.)

You also mentioned muscle wasting as a result of the prolonged use of relatively high dosages of thyroid hormone. We have not found an increase in serum or urine creatine in our patients on high thyroid hormone dosages. This rules out breakdown of lean tissue mass. Patients do lose a sall amount of weight, but this results from a slight degree of fat depletion associated with their increased activity levels. Certainly, it is not muscle wasting.You also warned of adverse cardiac effects.

We have performed hundreds of ECGs on hypothyroid and euthyroid fibromyalgia patients both before and during thyroid hormone therapy. Before treatment, the ECGs of many hypothyroid and euthyroid patients indicate a "hypothyroid heart." These results include low voltage deflections in the QRS complex, flattened or shallow inversion of T waves in all or most leads without comparable ST displacement, prolonged QT intervals, and sinus bradycardia. These ECG phenomena in our patients are corrected with thyroid hormone therapy. We have also found that treatment with the range of dosages you warn against has produced in our patients none of the classic "thyrotoxic heart effects" such as shortened QT interval, prolonged or shortened PR interval, ST segment elevation, U waves, or Wolfe-Parkinson-White syndrome. The genesis of the misguided concerns you expressed was a number of studies published in the early 1970s. Researchers tested patients taking 200-400 mcg of T4==common therapeutic dosages at the time, but dosages that suppressed the TSH level. They found "abnormal" values for a number of biochemical measures, and changes such as increased heart rate during sleep.

There was no evidence that these findings were harmful to the patients, but the researchers speculated that the findings would eventually lead to significant health problems. They advised clinicians not to permit patients to take more than 100 to 200 mcg==the amount that keeps the TSH within the normal range. Clinicians complied, and as a result, we read statements by clinicians such as yourself, advising patients to get their TSH levels checked. (You wrote:To find out whether your thyroid function is normal, ask your doctor to do a blood test to check your TSH level. The well-intended but scientifically unjustified conclusion that the only safe and effective T4 dosage is one that keeps the TSH within the normal range started in 1973. Since then, complaints by patients that these dosages leave them symptomatic have become legend.

It is a sad commentary on modern medical practice that clinicians now strive for a mid-range TSH and ignore the fact that it leaves many patients suffering==all because of a speculation made almost 25 years ago that has failed to be supported by subsequent scientific studies.

I want to emphasize for you: studies have not confirmed the conjecture that dosages of 200-400mcg cause patients any harm. Quite to the contrary, some studies have shown that these dosages are the only ones that benefit many patients. Still, though, most patients are denied the opportunity to determine whether such dosages are beneficial for them. The reason is that this speculation has now become entrenched in the unquestioning minds of many clinicians. As a result, hypothyroid patients the world over, including hypothyroid fibromyalgia patients, live a life of hell because of what I call the tyranny of the TSH.

Certainly, each patient must be considered on an individual basis, which we do at the Fibromyalgia Research Foundation. But in general, the scientific evidence does not support the conjecture that patients taking 200-400 mcg of thyroid hormone will be harmed by these amounts. I only wish that physicians had the same concern for the potentially harmful effects of patients not being treated with thyroid hormone when it is needed, or with denying them a high enough dosage. These possible effects include elevated cholesterol and triglycerides, hypertension, enlarged heart, ischemic heart disease, vacuolated degeneration and fibrosis of the heart, congestive heart failure, primary biliary cirrhosis, learning disabilities, cognitive impairment, and suicidal depression. As Bastenie has written, having too little thyroid hormone is a destructive process.

You wrote in conclusion, "I think people should be very circumspect about following the advice of a doctor who prescribes thyroid hormones in these circumstances. Many professionals would regard it as bordering on malpractice. I can excuse your ignorance of medical history and the science of thyroidology. But I take offense at the last statement, which constitutes an authoritarian attempt at intimidation. I am a research scientist and logician. As such, I pride myself on basing my opinions and conclusions on credible evidence. I am fully prepared to defend with evidence from the scientific literature and the studies of my own research team, each and every statement I make. On the other hand, your statements are the mere parroting of the false conclusions of others. If you consider yourself scientifically oriented, then you have a responsibility to examine the evidence relevant to an issue you give advice on. You have a responsibility to make your advice conform to what the scientific evidence indicates. Otherwise, you violate ethical standards of scientific conduct, and in that case, it is you who may be guilty of a form of malpractice. Fibromyalgia patients have suffered enough from misinformation. Out of compassion for them, you should consider this before disseminating further scientifically invalid information to them. I suggest that you go to the primary sources, and with an open mind, infer for yourself exactly and only what the evidence dictates. Should you do this, I am confident that you will rectify the well-intended but misguided warning you posted to the OzME subscribers.

– Dr. John C. Lowe


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